| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fetal anomalies v1.140 | LNPK |
Lilian Downie gene: LNPK was added gene: LNPK was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: LNPK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LNPK were set to PMID: 30032983, PMID:35599435, https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcad222/7243438?login=true Phenotypes for gene: LNPK were set to Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum MIM#618090 Review for gene: LNPK was set to GREEN Added comment: Moderate to severe ID, majority of patients 10/15 have period of regression Epilepsy (myoclonic frequently) Structural brain anomalies 'ear of the lynx sign', callosal hypoplasia, mild brain including cerebellar atrophy. Microcephaly, macrocephaly and normal head circumference described. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4273 | FDXR |
Ain Roesley gene: FDXR was added gene: FDXR was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FDXR were set to 30250212; 28965846 Phenotypes for gene: FDXR were set to Auditory neuropathy and optic atrophy, MIM# 617717 Review for gene: FDXR was set to RED gene: FDXR was marked as current diagnostic Added comment: Bi-allelic variants in FDXR cause an autosomal recessive neurologic disorder characterised by onset of visual and hearing impairment in the first or second decades. Two individuals described with a more severe phenotype, including one with microcephaly. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3908 | MAPK1 |
Krithika Murali gene: MAPK1 was added gene: MAPK1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAPK1 were set to 32721402 Phenotypes for gene: MAPK1 were set to Noonan syndrome 13 - MIM#619087 Review for gene: MAPK1 was set to GREEN Added comment: Associated with Noonan syndrome including congenital heart defects. No new publications since last PanelApp review Aug 2020 -- Motta et al (2020 - PMID: 32721402) report on 7 unrelated individuals harboring de novo missense MAPK1 pathogenic variants. The phenotype corresponded to a neurodevelopmental disorder and - as the authors comment - consistently included DD, ID , behavioral problems. Postnatal growth delay was observed in approximately half. Hypertelorism, ptosis, downslant of palpebral fissures, wide nasal bridge as low-set/posteriorly rotated ears were among the facial features observed (each in 3 or more subjects within this cohort). Together with short/webbed neck and abnormalities of skin (lentigines / CAL spots) and growth delay these led to clinical suspicion of Noonan s. or disorder of the same pathway in some. Congenital heart defects (ASD, mitral valve insufficiency, though not cardiomyopathy) occurred in 4/7. Bleeding diathesis and lymphedema were reported only once. MAPK1 encodes the mitogen-activated protein kinase 1 (also known as ERK2) a serine/threonine kinase of the RAS-RAF-MEK-(MAPK/)ERK pathway. MAPK1 de novo variants were identified in all individuals following trio exome sequencing (and extensive previous genetic investigations which were non-diagnostic). The distribution of variants, as well as in silico/vitro/vivo studies suggest a GoF effect (boosted signal through the MAPK cascade. MAPK signaling also upregulated in Noonan syndrome). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2364 | TECPR2 |
Zornitza Stark changed review comment from: SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominent. Included due to mild CC abnormalities.; to: SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominent. Included due to mild CC abnormalities, though clinical presentation is predominantly post-natal. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2364 | TECPR2 |
Zornitza Stark changed review comment from: SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominent; to: SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominent. Included due to mild CC abnormalities. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2349 | MECR | Ain Roesley reviewed gene: MECR: Rating: RED; Mode of pathogenicity: None; Publications: 27817865, 33401012, 31137067, 31070877; Phenotypes: Childhood-onset dystonia with optic atrophy and basal ganglia abnormalities is an autosomal recessive neurologic disorder characterized by onset of involuntary movements in the first decade of life. Optic atrophy develops around the same time or slightly later. Severity is variable, and some patients lose independent ambulation. Brain imaging shows abnormalities in the basal ganglia. Cognition appears to be unaffected. 7 unrelated families reported.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1676 | CAD | Zornitza Stark Marked gene: CAD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1676 | CAD | Zornitza Stark Gene: cad has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1676 | CAD | Zornitza Stark Phenotypes for gene: CAD were changed from Uridine-responsive epileptic encephalopathy to Epileptic encephalopathy, early infantile, 50, MIM# MIM 616457 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1675 | CAD | Zornitza Stark Publications for gene: CAD were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1674 | CAD |
Zornitza Stark changed review comment from: Four unrelated families (two with same variant and Roma background, likely founder). Sources: Expert list; to: Four unrelated families (two with same variant and Roma background, likely founder). Onset in infancy. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1674 | CAD | Zornitza Stark edited their review of gene: CAD: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1632 | ACADS | Zornitza Stark Marked gene: ACADS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1632 | ACADS | Zornitza Stark Gene: acads has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1632 | ACADS | Zornitza Stark Phenotypes for gene: ACADS were changed from SHORT CHAIN ACYL-COA DEHYDROGENASE DEFICIENCY to Acyl-CoA dehydrogenase, short-chain, deficiency of, MIM# 201470 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1631 | ACADM | Zornitza Stark Marked gene: ACADM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1631 | ACADM | Zornitza Stark Gene: acadm has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1631 | ACADM | Zornitza Stark Phenotypes for gene: ACADM were changed from MEDIUM CHAIN ACYL-COENZYME A DEHYDROGENASE DEFICIENCY to Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM# 201450 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1446 | ACADS | Zornitza Stark reviewed gene: ACADS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Acyl-CoA dehydrogenase, short-chain, deficiency of, MIM# 201470; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1446 | ACADM | Zornitza Stark reviewed gene: ACADM: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM# 201450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.774 | ELOVL4 |
Belinda Chong changed review comment from: OMIM 614457: ISQMR is a severe autosomal recessive disorder characterised by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures. 5 unrelated families reported, seizures in at least 4 of the families. OMIM 133190: Skin lesion appear shortly after birth and tend to disappear in young adulthood. In a large French-Canadian family, 14/19 individuals with a missense variant presented with erythrokeratodermia variabilis (PMID:24566826). At least two other individuals reported with erythrokeratodermia (and SCA34) as a result of a missense variant (PMID:26258735; 30065956). OMIM 600110: Stargardt disease-3 (STGD3) is an autosomal dominant juvenile macular dystrophy with onset most commonly in the second decade of life. Fundus examination reveals macular pigmentary changes and yellow flecks. Fluorescein angiography shows macular retinal pigment epithelium (RPE) defects; to: OMIM 614457: ISQMR is a severe autosomal recessive disorder characterised by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures. 5 unrelated families reported, seizures in at least 4 of the families. OMIM 133190: Skin lesion appear shortly after birth and tend to disappear in young adulthood. In a large French-Canadian family, 14/19 individuals with a missense variant presented with erythrokeratodermia variabilis (PMID:24566826). At least two other individuals reported with erythrokeratodermia (and SCA34) as a result of a missense variant (PMID:26258735; 30065956). OMIM 600110: Stargardt disease-3 (STGD3) is an autosomal dominant juvenile macular dystrophy with onset most commonly in the second decade of life. Fundus examination reveals macular pigmentary changes and yellow flecks. Fluorescein angiography shows macular retinal pigment epithelium (RPE) defects |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.754 | CYP2U1 | Zornitza Stark changed review comment from: Neurodegenerative condition rather than truly ID.; to: Neurodegenerative condition with onset in the first decade. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.29 | ACADVL | Zornitza Stark Marked gene: ACADVL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.29 | ACADVL | Zornitza Stark Gene: acadvl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.29 | ACADVL | Zornitza Stark Phenotypes for gene: ACADVL were changed from VERY LONG CHAIN ACYL-COENZYME A DEHYDROGENASE DEFICIENCY to VLCAD deficiency, MIM# 201475 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.28 | ACADVL | Zornitza Stark reviewed gene: ACADVL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: VLCAD deficiency, MIM# 201475; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.17 | ACAD9 | Zornitza Stark Marked gene: ACAD9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.17 | ACAD9 | Zornitza Stark Gene: acad9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.17 | ACAD9 | Zornitza Stark Phenotypes for gene: ACAD9 were changed from ACYL-COA DEHYDROGENASE FAMILY MEMBER TYPE 9 DEFICIENCY to Mitochondrial complex I deficiency, nuclear type 20, MIM# 611126 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.16 | ACAD9 | Zornitza Stark reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: 26475292; Phenotypes: Mitochondrial complex I deficiency, nuclear type 20, MIM# 611126; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | CAD |
Zornitza Stark gene: CAD was added gene: CAD was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CAD were set to Uridine-responsive epileptic encephalopathy |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | ACADS |
Zornitza Stark gene: ACADS was added gene: ACADS was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: ACADS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ACADS were set to SHORT CHAIN ACYL-COA DEHYDROGENASE DEFICIENCY |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | ACADM |
Zornitza Stark gene: ACADM was added gene: ACADM was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: ACADM was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ACADM were set to MEDIUM CHAIN ACYL-COENZYME A DEHYDROGENASE DEFICIENCY |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | ACADVL |
Zornitza Stark gene: ACADVL was added gene: ACADVL was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ACADVL was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ACADVL were set to VERY LONG CHAIN ACYL-COENZYME A DEHYDROGENASE DEFICIENCY |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | ACAD9 |
Zornitza Stark gene: ACAD9 was added gene: ACAD9 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ACAD9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACAD9 were set to 26475292 Phenotypes for gene: ACAD9 were set to ACYL-COA DEHYDROGENASE FAMILY MEMBER TYPE 9 DEFICIENCY |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||